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Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the oral cavity and is associated with high morbidity and mortality. Attention has been given to the role of inflammatory cells in carcinogenesis because of the ability of cancer cells to subvert the immune response. However, little is known about how molecules from neoplastic cells interact with lymphoblasts and circulating immune cells. This study aimed to understand the mechanisms by which SCC cells modulate the immune response by analyzing the influence of conditioned medium derived from SCC cell lines on immune cells.Lymphoblastic cells (CEM) and peripheral blood mononuclear cells (PBMC) were cultured in a conditioned medium derived from squamous cell carcinoma cells (SCC9 or SCC4) and analyzed for cell viability, CD4/CD8/FOXP3 profile by flow cytometry, and chemokine levels.Conditioned medium derived from SCC4 and SCC9 presented higher concentrations of IL-6 and IL-8 than IL-1β, IL-10, and IFN-γ. CEM and PBMCs when cultured with conditioned medium derived from SCC4 and SCC9 reduced IL-1β, IL-8, and IFN-γ concentrations. Conditioned medium from SCC4 increased CD4Collectively, our results suggest that the products derived from squamous cell carcinoma on inflammatory cells can promote an immunosuppressed environment by reducing cell viability, changing cytokine expression, and altering the cell immunoprofile.

Introduction: Nowadays, several bacteria have acquired resistance to available antimicrobial agents making necessary the search for new therapeutic alternatives. Plectranthus amboinicus L. is a succulent and aromatic herb, popularly known as thick leaf mint, used in popular medicine for the treatment of colds, digestive diseases, asthma, headache and to fight pathogenic bacteria activity. In view the antimicrobial activity of P. amboinicus this study had as aim to review publications involving researches about antimicrobial activity of this species. Materials and Methods: For this, PubMed, Scopus, Science Direct and Scielo databases were consulted in November 2020 using the keywords Plectranthus amboinicus and antimicrobial activity. In vitro and/or in vivo studies on the antimicrobial activity of the species in the last 10 years were considered. Results: The main microorganisms evaluated were: Klebsiella pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and some Candida species. The essential oils had carvacrol, germacrene D, thymol and camphor as main constituents. Most studies evaluated the antimicrobial activity using broth dilution and agar diffusion methods. In most studies essential oil, extracts and/or isolated substances showed significant antimicrobial activity. Synergistic activity was also observed through association with antibiotics. Conclusion: P. amboinicus has therapeutic potential for antimicrobial treatments and can be an alternative to the treatment of resistant microorganisms and that further in vivo and clinical studies with the species are still needed.

EXEMPLIFYING THE USE OF MACRO ELEMENTAL MAPPING BY XRF (MA-XRF) SCANNING IN FORENSIC INVESTIGATION OF ARTWORKS. This work exemplifies the potential of employing macro elemental mapping by XRF (MA-XRF) scanning in the forensic investigation of artworks. The results of the investigation of two artworks of different styles and periods are presented and discussed. The images provided by MA-XRF scanning have information about the elemental distribution, which is related to pigments used in the artwork. These images bring different information such as: if there are underlying paintings; if a given pigment was used for the purpose of restoration or in the creation. Therefore, through the images, it is possible to obtain information, which refers to the process of creating the artwork and the history of conservation and restoration. Through the results, it was possible to verify that the two artworks are probably false because they present anachronistic pigments with the supposed period of creation. The analyzes were performed using a portable MA-XRF scanning system, and in addition to presenting the utility of the instrument in these investigations, the work also presents possibilities to explore the MA-XRF data through multivariate statistical analysis and image correlation.

It is largely known that photobiomodulation (PBM) has beneficial effects on allergic pulmonary inflammation. Our previous study showed an anti-inflammatory effect of the PBM in an acute experimental model of asthma, and we see that this mechanism is partly dependent on IL-10. However, it remains unclear whether the activation of regulatory T cells is mediated by PBM in a chronic experimental model of asthma. In this sense, the objective of this study was to verify the anti-inflammatory role of the PBM in the pulmonary inflammatory response in a chronic experimental asthma model. The protocol used for asthma induction was the administration of OVA subcutaneously (days 0 and 14) and intranasally (3 times/week, for 5 weeks). On day 50, the animals were sacrificed for the evaluation of the different parameters. The PBM used was the diode, with a wavelength of 660 nm, a power of 100 mW, and 5 J for 50 s/point, in three different application points. Our results showed that PBM decreases macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid (BALF). Moreover, PBM decreased the release of cytokines by the lung, mucus, and collagen in the airways and pulmonary mechanics. When we analyzed the percentage of Treg cells in the group irradiated with laser, we verified an increase in these cells, as well as the release of IL-10 in the BALF. Therefore, we conclude that the use of PBM therapy in chronic airway inflammation attenuated the inflammatory process, as well as the pulmonary functional and structural parameters, probably due to an increase in Treg cells.

Snakebites caused by the genus Bothrops are often associated with severe and complex local manifestations such as edema, pain, hemorrhage, and myonecrosis. Conventional treatment minimizes the systemic effects of venom; however, their local action is not neutralized. The purpose of this study was to evaluate the effect of photobiomodulation (PBM) on C2C12 muscle cells exposed to B. jararaca, B. jararacussu, and B. moojeni venoms on events involved in cell death and the release of inflammatory mediators. Cells were exposed to venoms and immediately irradiated with low-level laser (LLL) application in continuous wave at the wavelength of 660 nm, energy density of 4.4 J/cm2, power of 10 mW, area of 0.045 cm2, and time of 20 s. Cell integrity was analyzed by phase contrast microscope and cell death was performed by flow cytometry. In addition, interleukin IL1-β, IL-6, and IL-10 levels were measured in the supernatant. Our results showed that the application of PBM increases cell viability and decreases cell death by apoptosis and necrosis. Moreover, the release of pro-inflammatory interleukins was also reduced. The data reported here indicate that PBM resulted in cytoprotection on myoblast C2C12 cells after venom exposure. This protection involves the modulation of cell death mechanism and decreased pro-inflammatory cytokine release.

Peganum harmala belongs to the family Zygophyllaceae and is popularly known as "Arruda of Syria". It presents a broad therapeutic potential, highlighting the anti inflammatory, anticancer, analgesic, antiseptic and antibacterial activities. It is used in the preparation of religious rituals beverages with effects on the central nervous system as an inhibitor of the enzyme monoaminoxidase, whose action is due to the presence of harmonic alkaloids of the β–carbolines group, with harmine and harmaline being the most found in P. harmala seeds. The objective of this study was to evaluate the chemical and pharmacognostic characteristics of P. harmala seeds with the aid of gas chromatography coupled to mass spectrometry. Pharmacognostic characterization was performed following the 5th edition of the Brazilian Pharmacopoeia. Scanning electron microscopy coupled to X-ray dispersive energy spectroscopy was performed for the seeds elemental identification. The compounds present in the species were identified by gas chromatography coupled to mass spectrometry. Phytochemical evaluation demonstrated the major secondary metabolites. The scanning electron microscopy coupled to X-ray dispersive energy spectroscopy analysis showed the morphology of the surface and interior of the seeds, as well as the atomic chemical analysis of the structures. By gas chromatography coupled to mass spectrometry, the chemical profile of P. harmala seeds was identified and the β–carbolines (harmaline and harmine) were identified, which are compounds of great pharmacological importance for the species. Therefore, it is concluded that this study is of great contribution to the plant material standardization that will serve as the basis for the future development of a pharmaceutical product. Key words: Arruda of Syria, characterization, gas chromatography, β-carbolines, Peganum harmala.

Background Most patients with head and neck cancer receive nonsteroidal anti-inflammatory drugs concomitant with oncogenic treatment in order to control cardiovascular diseases and chronic inflammatory processes. Inflammation is closely related to neoplastic development and the release of inflammatory cytokines and chemokines represents a crucial event in this relationship. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) and celecoxib treatment in the gene expression pattern of cytokines and chemokines in squamous cell carcinoma (OSCC) cell lines. Materials and methods Cells were treated with plasmatic concentrations of ASA and celecoxib and were submitted to cell viability assay and immunoenzymatic assay to investigate interleukin 6 (IL6) production. Treated cells were collected and a gene expression array was performed using the reverse transcriptase-quantitative polymerase chain reaction. Results Both treatments provoked a discrete inhibitory effect on cell viability and modulated IL6 production. The mRNA expression of several cytokines, chemokines, chemokine receptors, and other chemotaxis-related genes were modulated after treatment with ASA and celecoxib. Conclusion Plasmatic doses of ASA and celecoxib altered the expression of IL6 and the gene expression of chemokines (ligands and receptors) and cytokines in a dose- and time-dependent manner.

Photodamage is a growing concern in contemporary society, as it promotes premature skin aging and different pathologies resulting from prolonged and repeated exposure to ultraviolet solar radiation, which is considered the main extrinsic factor of this process. Affected by radiation, the hands have an important role in the manifestation and visibility of aging because they are very exposed body regions. The study proposal is developed by the potential mechanism of tissue repair, skin rejuvenation, anti-inflammatory and analgesic effects of photobiomodulation, complementing the benefits of chemical peel. The main objective of this randomized, controlled, double-blind clinical trial is to compare the photorejuvenating effects of 20% trichloroacetic acid (TCA) peel applied alone and the effects of the association of 20% TCA peel with 660nm light emitting diode (LED) photobiomodulation (PBM) in the treatment of the back of the hands. Participants will be divided into 2 groups and will receive different therapies according to the allocation group. Group A will be subjected to 04 chemical peel sessions of 20% TCA and PBM. Group B will also receive the 04 chemical peel sessions of 20% TCA with PBM simulation. The application sessions will be monthly and the consultations for fortnightly evaluations. Analysis of photoaging characteristics such as fine and coarse wrinkles, dyschromias and global assessment of the back of the hands will be carried out using periodic standardized photographs. A visual-analog pain scale and a 5-point Likert scale will also be applied regularly to assess participants' satisfaction.

Mimosa tenuiflora (Willd.) Poir., popularly known as “black jurema”, is a plant that is predominant in the Caatinga Biome. Drinks used in indigenous rituals use the barks of this plant that are rich in N,N-dimethyltryptamine (DMT), an indolic alkaloid responsible for hallucinogenic activity. The objective of this study was to evaluate the chemical and pharmacognostic characteristics of the Mimosa tenuiflora bark using nuclear magnetic resonance(NMR) analytical techniques and gas chromatography coupled to mass spectrometry(GC-MS) to identify and quantify the DMT present in the extract of Mimosa tenuiflora. The results showed that the plant material is within the recommended standards. Both NMR and GC-MS techniques were able to identify and quantify the DMT with NMR being the best option. In conclusion this study contributes significantly to the standardization of the studied plant material and assists in the use of these data for future development of products from on this forestry species.

Spondias tuberosa Arruda (Anacardiaceae) is an endemic tree in the Caatinga Brazilian Biome, known locally as "umbuzeiro" and used for various purposes, especially as food and folk medicine. In this study, it was realized for the first time, the extraction and characterization by gas chromatography-mass spectrometry (GC-MS) of the fixed oils of barks, leaves and stems of S. tuberosa. The constituents of the oils were identified by comparing the mass spectra obtained with those of the equipment database. The major component of fixed oil obtained from barks was the 3-n-Pentadecylphenol (44.91 %), in the leaves and stems was observed presence of the tetratetracontane (38.17 and 28.57%, respectively). Antioxidant activity was evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and β-carotene-linoleic acid bleaching test. The fixed oil obtained from the leaves presented the best antioxidant activity (51.13%±11.8) in β-carotene-linoleic acid bleaching test. This study described for the first time identification and quantification of the components present in the fixed oils of the bark, leaves and stems of Spondias tuberosa. Key words: Natural products, fatty acids, gas chromatography-mass spectrometry (GC-MS), antioxidant.

Background: Pseudomonas aeruginosa (PS) infection results in severe morbidity and mortality, especially in immune-deficient populations. Aerobic exercise (AE) modulates the immune system, but its effects on the outcomes of pulmonary PS infection in elderly mice are unknown. Methods: BALB/c mice (24 weeks old) were randomized to sedentary, exercise (EX), PS, and PS + EX groups for the acute experimental setting, and PS and PS + EX groups for the chronic setting. Low-intensity AE was performed for 5 weeks, 60 min/day; 24 h after the final AE session, mice were inoculated with 5 × 104 colony-forming units (CFU) of PS, and 24 h and 14 days after PS inoculation, mice were studied. Results: AE inhibited PS colonization (p < 0.001) and lung inflammation (total cells, neutrophils, lymphocytes [p < 0.01] in bronchoalveolar lavage [BAL]), with significant differences in BAL levels of IL-1β (p < 0.001), IL-6 (p < 0.01), CXCL1 (p < 0.001), and TNF-α (p < 0.001), as well as parenchymal neutrophils (p < 0.001). AE increased BAL levels of IL-10 and parenchymal (p < 0.001) and epithelial (p < 0.001) IL-10 expression, while epithelial (p < 0.001) and parenchymal (p < 0.001) NF-κB expression was decreased. AE diminished pulmonary lipid peroxidation (p < 0.001) and increased glutathione peroxidase (p < 0.01). Pre-incubation of BEAS-2B with IL-10 inhibited PS-induced epithelial cell expression of TNF-α (p < 0.05), CD40 (p < 0.01), and dichlorodihydrofluorescein diacetate (p < 0.05). Conclusions: AE inhibits PS-induced lung inflammation and bacterial colonization in elderly mice, involving IL-10/NF-κB, and redox signaling.

Purpose: We have previously shown that domperidone-induced short-term hyperprolactinemia reduces the lung’s allergic inflammatory response in an ovalbumin antigenic challenge model. Since purinergic receptor P2X7R activity leads to proinflammatory cytokine release and is possibly related to the pathogenesis of allergic respiratory conditions, the present study was designed to investigate a possible involvement of purinergic and prolactin receptors in this phenomenon. Methods: To induce hyperprolactinemia, domperidone was injected intraperitoneally in rats at a dose of 5.1 mg × kg–1 per day for 5 days. P2X7 expression was evaluated by lung immunohistochemistry while prolactin receptor expression in bronchoalveolar lavage leukocytes was analyzed through flow cytometry. Results: Previous reports demonstrated that rats subjected to short-term hyperprolactinemia exhibited a decrease in leukocyte counts in bronchoalveolar lavage, especially granulocytes. Here, it is revealed that hyperprolactinemia promotes an increased expression of prolactin receptors in granulocytes. Also, increased expression of purinergic P2X7R observed in allergic animals was significantly reduced by hyperprolactinemia. Conclusions: Both purinergic and prolactin receptor expression changes occur during the anti-asthmatic effect of hyperprolactinemia.

Annona vepretorum Mart. is a medicinal plant endemic to Brazil, popularly known as "araticum", “bruteira” and “pinha da Caatinga”. In this study, the chemical composition of different leaf extracts obtained from this species was evaluated. Chemical compounds were isolated by silica gel column chromatography, resulting in a mixture of steroids (β-sitosterol and stigmasterol) and a triterpene (lupeol acetate). Ethanol extract presented a precipitate insoluble in chloroform, which after washing was identified as the flavonoid rutin quercetin-3-O-α-L-rhamnopyranosyl-(1'''→6'')-β-glucopyranoside). These compounds are being reported for the first time in A. vepretorum. Key words: Annona vepretorum, leaf extracts, phytochemical investigation, 1H and 13C NMR.

Lung fibrosis (LF) is a chronic and progressive lung disease characterized by pulmonary parenchyma progressive lesion, inflammatory infiltration, and interstitial fibrosis. It is developed by excessive collagen deposition and other cellular matrix components, resulting in severe changes in the alveolar architecture. Considering the absence of effective treatment, the aim of this study was to investigate the effect of photobiomodulation therapy (PBMT) on the development of PF. For this purpose, we used C57BL6 mice subjected to induction of LF by bleomycin administration (1.5 U/kg) by orotracheal route and, after 14 days of the induction, mice were treated with PBMT applied to the thorax 1×/day for 8 days (wavelength 660 ± 20 nm, power 100 mW, radiant exposure 5 J/cm2, irradiance 33.3 mW/cm2, spot size 2.8cm2, total energy 15 J, time of irradiation: 150 s) and inflammatory and fibrotic parameters were evaluated with or without PBMT. Our results showed that PBMT significantly reduced the number of inflammatory cells in the alveolar space, collagen production, interstitial thickening, and static and dynamic pulmonary elastance. In addition, we observed reduced levels of IL-6 e CXCL1/KC released by pneumocytes in culture as well as reduced level of CXCL1/KC released by fibroblasts in culture. We can conclude that the PBMT improves both inflammatory and fibrotic parameters showing a promising therapy which is economical and has no side effects.

Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are known to modulate a variety of immune cell functions. On occasion, this has led to diminished host resistance to certain viral and bacterial infections. Little is known about the impact of n-3 PUFA on host resistance to parasitic infection, however, based on results from a small study conducted more than two decades ago, we hypothesized that providing mice LC n-3 PUFA will diminish host resistance to Trypanosoma cruzi, the parasitic pathogen responsible for Chagas disease. To investigate this, C57BL/6 mice were supplemented by gavage (0.6% v/w) with phosphate-buffered saline, corn oil (CO), or menhaden fish oil (FO, a fat source rich in LC n-3 PUFA) for 15 days prior to T cruzi (Y strain) challenge and throughout the acute phase of infection. FO supplementation was associated with a transient 2-fold greater peak of blood parasitemia at 7 days postinfection (dpi), whereas subsequent cardiac parasitemia was ~60% lower at 12 dpi. FO treatment also ameliorated the leukopenia and thrombocytopenia observed in the early stages of a T cruzi infection. FO supplementation reduced circulating and cardiac nitric oxide at 7 and 12 dpi, respectively. FO supplementation altered ex vivo prostaglandin E2 and cytokine and chemokine production by splenocytes isolated from uninfected and infected mice. Overall, our results suggest that oral administration of LC n-3 PUFA from FO can have beneficial effects on the host in the early course of a T cruzi infection.

Simira gardneriana is a Rubiaceae species commonly found in the Brazilian Northeast region, presented several therapeutic and biotechnological applications. In this paper, the antioxidant and photoprotective properties of extracts from the seeds of S. gardneriana were highlighted. The antioxidant activity of ethanol and methanol extracts (Si-EtOH and Si-MeOH, respectively) was determined, using 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging assay. The photoprotective activity of the extracts was evaluated using a spectrophotometric method. Total phenolic and flavonoid content was determined. In addition, a qualitative analysis of phytochemical markers and a high-performance liquid chromatography-diode-array detector (HPLC-DAD) analysis were also performed for both extracts. Concerning the antioxidant activity in vitro, Si-MeOH (EC50 = 70.94±2.17 µg/ml) showed greater activity in comparison to Si-EtOH (EC50 = 138.60±7.39 µg/ml). Once the sun protection factor spectrophotometric (SPFspectrophotometric) of samples was calculated, it was demonstrated that the extracts show a similar photoprotective effect on all concentrations tested. Si-EtOH and Si-MeOH tested on a concentration of 100 mg/l, exhibited SPF values equal to 3.37±0.006 and 3.36±0.007, respectively. HPLC fingerprints was recorded and showed the presence of characteristic peaks for phenolic compounds. The extracts showed significant phenols and flavonoids content according to the quantification methods used. According to the results, it was concluded that Si-EtOH and Si-MeOH have significant antioxidant and photoprotective activities. These activities are probably related to the profile of flavonoids and phenolic compounds found in this species. Key words: Phenolic and flavonoids compounds, photoprotective, oxidative stress, plant, Rubiaceae.

Since asthma is a multifactorial disease where treatment sometimes is not effective, new therapies that improve the respiratory discomfort of patients are of great importance. Phototherapy as Light-emitting diode (LED) has emerged as a treatment that presents good results for diseases that are characterized by inflammation. Thus, our objective was to investigate the effects of LED on lung inflammation, by an evaluation of lung cell infiltration, mucus secretion, oedema, and the production of cytokines. Male Balb/c mice were or not sensitized and challenged with ovalbumin (OVA) and treated or not with LED therapy (1 h and 4 h after each OVA challenge). Twenty-four hours after the last OVA challenge, analyzes were performed. Our results showed that LED treatment in asthmatic mice reduced the lung cell infiltration, the mucus production, the oedema, and the tracheal's contractile response. It also increased the IL-10 and the IFN-gamma levels. The effects of LED treatment on lung inflammation may be modulated by IL-10, IFN-gamma, and by mast cells. This study may provide important information about the effects of LED, and in addition, it may open the possibility of a new approach for the treatment of asthma.

Acute respiratory distress syndrome (ARDS) is characterized by acute lung inflammation involving both the recruitment and activation inflammatory cells as well as the release of inflammatory factor...

Probiotics can be considered nonspecific adjuvants of innate immune response by modulating the Th1/Th2 response in different pathological conditions. Our goal is to investigate the probiotic Lactobacillus bulgaricus (Lb) anti-inflammatory effect in experimental asthma. BALB/c-mice were sensitized with ovalbumin (OVA) on days 0 and 7 and then were challenged from day 14-28 (3-times/week) with aerosolized OVA. From seventh day before the sensitization until day 28, mice were treated 3-times/ week with Lb via gavage. All measurements were performed 24 hours after the last OVA challenge. The CD86 molecules expression as well as the toll-like 4 receptor on dendritic cells was increased after oral administration of Lb. In addition, Lb attenuated the eosinophils infiltration, mucus production and the ovalbumin-specific IgE concentration in serum. Moreover, Lb inhibited the secretion of asthma-related inflammatory molecules such as IL-4, IL-5, IL-13 and eotaxin in bronchoalveolar lavage fluid (BALF). On the contrary, the IL-10 level in BALF was reduced by Lb. The analysis of lung tissue using real-time PCR revealed that Lb inhibited the local transcription of asthma-associated genes such as GATA3 and STAT6, and the otherwise Lb increased the expression of T-bet. The results contribute to the understanding of the probiotic modulator activities for the control of allergic diseases.

Recent studies show that low-level laser therapy (LLLT) has an important anti-inflammatory action in acute lung inflammation. The present work explored if laser therapy is able to antagonize eosinophils and allergic inflammation induced by oxidative stress in Balb/c mice. Forty-eight hours after challenge, the leukocyte counting, ROS and nitrite/nitrate level, RANTES, CCL3, CCL8 as well as eotaxins were measured in the bronchoalveolar lavage fluid (BALF) of laser-treated mice or not. Into the lung, some chemokines receptors, the iNOS activity and mRNA expression, and the activities of superoxide dismutase (SOD), catalase, gluthatione, NADPH oxidase activities and thiobarbituric acid reactive species (T-Bars) were measured. Laser-treated allergic mice presented reduction of both the ICAM-1 and eosinophil in the lungs. RANTES, CCL8, CCL3 and eotaxins were reduced in BALF of laser-treated allergic mice. In allergic mice lung LLLT decreased the CCR1 and CCR3 and restored the oxidative stress balance as well. Laser decreased the lipidic peroxidation in allergic mice lung as much as increased SOD, GPx and GR. It shows that LLLT on allergic lung inflammation involves leukocyte-attractant chemokines and endogenous antioxidant. Based on results, LLLT may ultimately become a non- invasive option in allergic lung disease treatment. The top figure illustrates the laser decreasing the eosinophils migration into BALF and the bottom figure shows the laser upregulating the expression of heme-oxygenase (anti-oxidant enzyme) in lung tissue anti-oxidant.

Rubiaceae family includes many species with biological activity, highlighting the genus Simira. In the Caatinga, this genus is represented by six species, and among them, Simira gardneriana is the only endemic species. Previous studies with this plant have shown that extracts from the aerial parts have antioxidant and antimicrobial activity. Thus, the aim of this study was to investigate the chemical composition, antibacterial and cytotoxic activities of fixed oil and fatty acids fraction obtained from seeds of the plant. For this, the fixed oil (Si-FO) was obtained through an extraction with petroleum ether. Subsequently, the fraction of fatty acids (Si-FA) was obtained and then esterified to facilitate analysis by gas chromatography-mass spectrometry GC-MS. Si-FO and Si-FA were evaluated for their antibacterial (MIC and MBC determination) and cytotoxic (MTS assays) properties. The GC-MS analysis identified squalene (39.95%), β-sitosterol (13.82%) and palmitic aldehyde (7.02%) as the major components of Si-FO. Meanwhile, the major compounds identified for the methylated fatty acids fraction were oleic (51.17%), 5,6-octadecadienoic (16.22%) and stearic acids (10.47%). In terms of biological activity, Si-FO and Si-FA exhibited relevant antibacterial activity against Enterococcus faecalis, Escherichia coli and Bacillus cereus strains. In addition, Si-FO showed moderate cytotoxicity against Sarcome S-180 cells, reaching 50.58% of cytotoxic activity in the highest concentration tested (400 μg/ml). These results can be explained by the chemical composition of the samples, since previous studies reported antibacterial and cytotoxic effects of the major compounds identified in Si-FO and Si-FA. Key words: Fixed oil, fatty acids, antibacterial, cytotoxic, Rubiaceae, Simira, Caatinga.

The aim of this study was to verify the impact of periodontitis in the course of chronic obstructive pulmonary disease (COPD) in C57Bl/6J mice.The animals were randomly divided into four groups (n = 8): Basal, Periodontitis (P), COPD and COPD+P. COPD was induced by orotracheal instillation of 30 μl of cigarette extract 3 times/week for 7 weeks. Periodontitis was induced by ligation technique for 22 days. Euthanasia was performed on 51st day. The analyzes were total/differential cells and cytokines recovered from bronchoalveolar lavage (BAL), total/differential blood cell count, platelets, total marrow cell count, airway collagen deposition, alveolar enlargement analyzed by mean linear intercept (Lm), mucus and bone crest reabsorption. One-way ANOVA followed by the Student-Newman-Keuls was used.The association COPD+P decreased macrophages (p = 0,0351), TNF-α (p = 0,0071) and INF-γ (p = 0,0004) in BAL, when compared to the COPD group maintaining emphysema levels by alveolar enlargement (p .05) reorganization of collagen fibers (p = .001) and also mean linear intercept (lm) (p = .001) and mucus (p = .0001). The periodontitis group caused TNF-α increase (p = 0, 0001) in BAL.Periodontitis, per se, does not alter any of the parameters analyzed, except for increased TNF-α in BAL. However, its association with COPD caused macrophages TNF-α and INF-γ alterations, when compared to the COPD group maintaining emphysema levels by alveolar enlargement and reorganization of collagen fibers. It seems that periodontitis is influencing the course of Th1 profile cell, and cytokines and pulmonary alterations. Further studies are needed to clarify the regulatory process underlying these two diseases.

Amburana cearensis is an arboreal legume of the Fabaceae family, with high phytotherapic and medicinal potential due the presence of secondary metabolites. The objective of this study was to evaluate the effect of 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-amino-2,5,6- trichloro-2-pyridinecarboxylic acid (picloram) on the in vitro induction of callogenesis of A. cearensis and analyze the biochemical and phytochemical potential of these calluses. For callus induction, leaf and cotyledon segments were used as explants, which were inoculated in woody plant medium (WPM) supplemented with different concentrations of 2,4-D (0, 5, 10, 20, 40 μM) or picloram (0, 5, 10, 20, 40, 80 μM). The callus growth curve was estimated based on fresh weight, measured at 7-day intervals until 28 days after inoculation. The calluses were analyzed by biochemical tests to quantify the reducing sugars and total proteins. Phytochemical screening and high-performance liquid chromatography were performed to establish the phytochemical profile of extracts from calluses. The concentrations of 21.94 μM and 26.46 μM of 2,4-D induced the greatest formation of compact and friable calluses from the leaf and cotyledon segments, respectively. The growth curve had two distinct phases (lag and exponential) for both types of calluses evaluated. The maximum levels of reducing sugars and total proteins in the calluses from leaf and cotyledon segments were obtained on the day of inoculation and after 28 days of cultivation, respectively. The results of the phytochemical analysis identified the presence of coumarin in all the extracts evaluated, this secondary metabolite has high pharmacological potential. Amburana cearensis is an arboreal legume of the Fabaceae family, with high phytotherapic and medicinal potential due the presence of secondary metabolites. The objective of this study was to evaluate the effect of 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-amino-2,5,6- trichloro-2-pyridinecarboxylic acid (picloram) on the in vitro induction of callogenesis of A. cearensis and analyze the biochemical and phytochemical potential of these calluses. For callus induction, leaf and cotyledon segments were used as explants, which were inoculated in woody plant medium (WPM) supplemented with different concentrations of 2,4-D (0, 5, 10, 20, 40 μM) or picloram (0, 5, 10, 20, 40, 80 μM). The callus growth curve was estimated based on fresh weight, measured at 7-day intervals until 28 days after inoculation. The calluses were analyzed by biochemical tests to quantify the reducing sugars and total proteins. Phytochemical screening and high-performance liquid chromatography were performed to establish the phytochemical profile of extracts from calluses. The concentrations of 21.94 μM and 26.46 μM of 2,4-D induced the greatest formation of compact and friable calluses from the leaf and cotyledon segments, respectively. The growth curve had two distinct phases (lag and exponential) for both types of calluses evaluated. The maximum levels of reducing sugars and total proteins in the calluses from leaf and cotyledon segments were obtained on the day of inoculation and after 28 days of cultivation, respectively. The results of the phytochemical analysis identified the presence of coumarin in all the extracts evaluated, this secondary metabolite has high pharmacological potential.

The association of Periodontitis (P) with several systemic diseases, among them asthma (A), has been previously studied. As periodontal treatment (TTO) associated with photodynamic therapy (PDT) is able to treat P, the aim of this study is to verify whether periodontitis exerts systemic effects on asthma, and whether TTO, associated or not with PDT, is capable of altering the systemic course of both pathologies.64 male Balb/c mice were divided into 8 groups (n = 8): Basal (B), P, P + TTO, P + TTO + PDT, Asthma, A + P, A + P + TTO, A + P + TTO + PDT. After 43 days, all animals were euthanized. The total and differential leukocyte count in serum, platelet count, alveolar bronchial lavage cell count, femoral lavage cell count in addition to the reactivity of the trachea, lung edema and gingiva cytokines were analyzed. The frequency of inflammatory cells was assessed via flow cytometry. One-way ANOVA test was used, followed by the Student-Newman-Keuls post-test.There was an increase in the number of blood circulating eosinophils in group A when compared to group B (p 0.01); this characterized the asthma experimental model. P (p 0.05) presented a lower amount of cytokine TNF-α in the gingiva when compared to the Asthma group. Apart from that, there was no statistical difference found for the other analyzed parameters.These data contributed to elucidate that P and A, associated or not with TTO and PDT, are not able to interfere with the systemic parameters of Balb/c mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic inflammatory disease with a poor prognosis and very few available treatment options. Low-level laser therapy (LLLT) has been gaining prominence as a new and effective anti-inflammatory and immunomodulatory agent. Can lung inflammation and the airway remodeling be regulated by LLLT in an experimental model of IPF in C57Bl/6 mice? The present study investigated if laser attenuates cellular migration to the lungs, the airway remodeling as well as pro-fibrotic cytokines secretion from type II pneumocytes and fibroblasts. Mice were irradiated (780 nm and 30 mW) and then euthanized fifteen days after bleomycin-induced lung fibrosis. Lung inflammation and airway remodeling were evaluated through leukocyte counting in bronchoalveolar lavage fluid (BALF) and analysis of collagen in lung, respectively. Inflammatory cells in blood were also measured. For in vitro assays, bleomycin-activated fibroblasts and type II pneumocytes were irradiated with laser. The pro- and anti-inflammatory cytokines level in BALF as well as cells supernatant were measured by ELISA, and the TGFβ in lung was evaluated by flow cytometry. Lung histology was used to analyze collagen fibers around the airways. LLLT reduced both migration of inflammatory cells and deposition of collagen fibers in the lungs. In addition, LLLT downregulated pro-inflammatory cytokines and upregulated the IL-10 secretion from fibroblasts and pneumocytes. Laser therapy greatly reduced total lung TGFβ. Systemically, LLLT also reduced the inflammatory cells counted in blood. There is no statistical difference in inflammatory parameters studied between mice of the basal group and the laser-treated mice. Data obtained indicate that laser effectively attenuates the lung inflammation, and the airway remodeling in experimental pulmonary fibrosis is driven to restore the balance between the pro- and anti-inflammatory cytokines in lung and inhibit the pro-fibrotic cytokines secretion from fibroblasts.

Sepsis is a big health problem and one of the most common causes of acute lung injury (ALI) leading to high mortality. Pro-resolving mediators play an important role in abrogating the inflammation and promoting tissue homeostasis restoration. ALI treatment is still a clinical health problem, so new therapies are needed. Here, we evaluated the effect of photobiomodulation treatment on the resolution process of ALI induced by lipopolysaccharide (LPS). Male Balb/c mice were submitted to LPS (ip) or vehicle and irradiated or not with light emitting diode (LED) 2 and 6 h after LPS or vehicle injection, and the parameters were investigated 3 and 7 days after the injections. Our results showed that after 3 days of LED treatment the blood and bronchoalveolar lavage (BAL) cells as well as interleukins (IL) including IL-6 and IL-17 were reduced. No differences were observed in the bone marrow cells, tracheal reactivity, and lipoxin A4 and resolvin E2. Indeed, after 7 days of LED treatment the bone marrow cells, lymphocytes, and lipoxin A4 were increased, while IL-6, IL-17, and IL-10 were decreased. No differences were observed in the blood cells and tracheal reactivity. Thus, our results showed that LED treatment attenuated ALI induced by sepsis by modulating the cell mobilization from their reserve compartments. In addition, we also showed later effects of the LED up to 7 days after the treatment. This study proposes photobiomodulation as therapeutic adjuvant to treat ALI.

Acute respiratory distress syndrome (ARDS) is defined as hypoxemic respiratory failure with intense pulmonary inflammation, involving hyperactivation of endothelial cells and neutrophils. Given the anti-inflammatory effects of aerobic exercise (AE), this study investigated whether AE performed daily for 5 weeks would inhibit extra-pulmonary LPS-induced ARDS. C57Bl/6 mice were distributed into Control, Exercise, LPS and Exercise+LPS groups. AE was performed on a treadmill for 5x/week for four weeks before LPS administration. 24hours after the final AE physical test, animals received 100ug of LPS intra-peritoneally. In addition, whole blood cell culture, neutrophils and human endothelial cells were pre-incubated with IL-10, an anti-inflammatory cytokine induced by exercise. AE reduced total protein levels and neutrophil accumulation in bronchoalveolar lavage (BAL) and lung parenchyma. AE reduced BAL inflammatory cytokines IL-1β, IL-6 and GM-CSF (p

Asthma is characterized by chronic inflammation in the airways. Several models have been proposed for the discovery of new therapies. Low-Level Laser Therapy (LLLT) is relatively new and effective, very low cost, with no side effects. However, there is still no consensus on the optimal dose to be used. In this sense, the objective of the present study was to evaluate the best dose in an experimental model of asthma induced by House Dust Mite (HDM). Balb/c mice received administration of 100 ug/animal HDM and LLLT applications (diode laser: 660 nm, 100 mW and four different energies 1J, 3J, 5J, and 7.5J) for 16 days. After 24 hours, we studied inflammatory, functional, and structural parameters. The results showed that LBI was able to modulate the pulmonary inflammation observed by reducing the number of cells in Bronchoalveolar Lavage Fluid (BALF) as well as reducing the percentage of neutrophils, eosinophils and T lymphocytes. On the other hand, LLLT increased the level of IL-10 and reduced levels of IL-4, IL-5 and IL-13 in BALF. LLLT was able to reduce the production of mucus, peribronchial eosinophils, collagen deposition, bronchoconstriction index, and bronchial and muscular thickening in the airways. We concluded that the use of LLLT in the treatment of chronic inflammation of the airways attenuated the inflammatory process and functional and structural parameters. We emphasize, in general, that the 1J and 3J laser presented better results. Thus, photobiomodulation may be considered a promising tool for the treatment of chronic pulmonary allergic inflammation observed in asthma.

The present study was aimed to investigate the phototherapy effect with low-level laser on human bronchial epithelial cells activated by cigarette smoke extract (CSE). Phototherapy has been reported to actuate positively for controlling the generation/release of anti-inflammatory and pro-inflammatory mediators from different cellular type activated by distinct stimuli. It is not known whether the IL-8 and IL-10 release from CSE-stimulated human bronchial epithelium (BEAS) cells can be influenced by phototherapy. Human bronchial epithelial cell (BEAS) line was cultured in a medium with CSE and irradiated (660 nm) at 9 J. Apoptosis index was standardized with Annexin V and the cellular viability was evaluated by MTT. IL-8, IL-10, cAMP, and NF-κB were measured by ELISA as well as the Sp1, JNK, ERK1/2, and p38MAPK. Phototherapy effect was studied in the presence of mithramycin or the inhibitors of JNK or ERK. The IL-8, cAMP, NF-κB, JNK, p38, and ERK1/2 were downregulated by phototherapy. Both the JNK and the ERK inhibitors potentiated the phototherapy effect on IL-8 as well as on cAMP secretion from BEAS. On the contrary, IL-10 and Sp1 were upregulated by phototherapy. The mithramycin blocked the phototherapy effect on IL-10. The results suggest that phototherapy has a dual effect on BEAS cells because it downregulates the IL-8 secretion by interfering with CSE-mediated signaling pathways, and oppositely upregulates the IL-10 secretion through of Sp1 transcription factor. The manuscript provides evidence that the phototherapy can interfere with MAPK signaling via cAMP in order to attenuate the IL-8 secretion from CSE-stimulated BEAS. In addition, the present study showed that phototherapy effect is driven to downregulation of the both the IL-8 and the ROS secretion and at the same time the upregulation of IL-10 secretion. Besides it, the increase of Sp-1 transcription factor was crucial for laser effect in upregulating the IL-10 secretion. The dexamethasone corticoid produces a significant inhibitory effect on IL-8 as well as ROS secretion, but on the other hand, the corticoid blocked the IL-10 secretion. Taking it into consideration, it is reasonable to suggest that the beneficial effect of laser therapy on lung diseases involves its action on unbalance between pro-inflammatory and anti-inflammatory mediators secreted by human bronchial epithelial cells through different signaling pathway.

Pseudomonas aeruginosa (PS) infection results in severe morbidity and mortality, especially in immune-deficient populations. Aerobic exercise (AE) modulates the immune system, but its effects on the outcomes of pulmonary PS infection in elderly mice are unknown.BALB/c mice (24 weeks old) were randomized to sedentary, exercise (EX), PS, and PS + EX groups for the acute experimental setting, and PS and PS + EX groups for the chronic setting. Low-intensity AE was performed for 5 weeks, 60 min/day; 24 h after the final AE session, mice were inoculated with 5 × 104 colony-forming units (CFU) of PS, and 24 h and 14 days after PS inoculation, mice were studied.AE inhibited PS colonization (p0.001) and lung inflammation (total cells, neutrophils, lymphocytes [p0.01] in bronchoalveolar lavage [BAL]), with significant differences in BAL levels of IL-1β (p0.001), IL-6 (p0.01), CXCL1 (p0.001), and TNF-α (p0.001), as well as parenchymal neutrophils (p0.001). AE increased BAL levels of IL-10 and parenchymal (p0.001) and epithelial (p0.001) IL-10 expression, while epithelial (p0.001) and parenchymal (p0.001) NF-κB expression was decreased. AE diminished pulmonary lipid peroxidation (p0.001) and increased glutathione peroxidase (p0.01). Pre-incubation of BEAS-2B with IL-10 inhibited PS-induced epithelial cell expression of TNF-α (p0.05), CD40 (p0.01), and dichlorodihydrofluorescein diacetate (p0.05).AE inhibits PS-induced lung inflammation and bacterial colonization in elderly mice, involving IL-10/NF-κB, and redox signaling.

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by irreversible airflow limitation, airway inflammation and remodeling, and enlargement of alveolar spaces. COPD is in the top five leading causes of deaths worldwide and presents a high economic cost. However, there are some preventive measures to lower the risk of developing COPD. Low-level laser therapy (LLLT) is a new effective therapy, with very low cost and no side effects. So, our objective was to investigate if LLLT reduces pulmonary alterations in an experimental model of COPD. C57BL/6 mice were submitted to cigarette smoke for 75 days (2x/day). After 60 days to smoke exposure, the treated group was submitted to LLLT (diode laser, 660 nm, 30 mW, and 3 J/cm2) for 15 days and euthanized for morphologic and functional analysis of the lungs. Our results showed that LLLT significantly reduced the number of inflammatory cells and the proinflammatory cytokine secretion such as IL-1β, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF). We also observed that LLLT decreased collagen deposition as well as the expression of purinergic P2X7 receptor. On the other hand, LLLT increased the IL-10 release. Thus, LLLT can be pointed as a promising therapeutic approach for lung inflammatory diseases as COPD.

Obesity results in decreased lung function and increased inflammation. Moderate aerobic exercise (AE) reduced lung inflammation and remodeling in a variety of respiratory disease models. Therefore, this study investigated whether AE can attenuate a diet-induced obesity respiratory phenotype; including airway hyper-responsiveness (AHR), remodeling and inflammation.Sixty C57Bl/6 male mice were distributed into four groups: control lean (CL), exercise lean (EL), obese (O) and obese exercise (OE) groups (2 sets of 7 and 8 mice per group; n = 15). A classical model of diet-induced obesity (DIO) over 12 weeks was used. AE was performed 60 min/day, 5 days/week for 5 weeks. Airway hyperresponsiveness (AHR), lung inflammation and remodeling, adipokines and cytokines in bronchoalveolar lavage (BAL) was determined.A high fat diet over 18 weeks significantly increased body weight (p .0001). Five weeks of AE significantly reduced both AHR and pulmonary inflammation. AHR in obese mice that exercised was reduced at the basal level (p .05), vehicle (PBS) (p .05), 6.25 MCh mg/mL (p .05), 12.5 MCh mg/mL (p .01), 25 MCh mg/mL (p .01) and 50 MCh mg/mL (p .05). Collagen (p .001) and elastic (p .001) fiber deposition in airway wall and also smooth muscle thickness (p .001) were reduced. The number of neutrophils (p .001), macrophages (p .001) and lymphocytes (p .01) were reduced in the peribronchial space as well as in the BAL: lymphocytes (p .01), macrophages (p .01), neutrophils (p .001). AE reduced obesity markers leptin (p .001), IGF-1 (p .01) and VEGF (p .001), while increased adiponectin (p .01) in BAL. AE also reduced pro-inflammatory cytokines in the BAL: IL-1β (p .001), IL-12p40 (p .001), IL-13 (p .01), IL-17 (p .001, IL-23 (p .05) and TNF-alpha (p .05), and increased anti-inflammatory cytokine IL-10 (p .05).Aerobic exercise reduces high fat diet-induced obese lung phenotype (AHR, pulmonary remodeling and inflammation), involving anti-inflammatory cytokine IL-10 and adiponectin.

Idiopathic pulmonary fibrosis (IPF) is characterized by decline of lung function, inflammation and fibrosis. Previous studies demonstrated that aerobic exercise (AE) can accelerate the resolution of lung fibrosis in a model of bleomycin-induced lung fibrosis. However, the effects of AE on lung response when beginning at the same time of bleomycin administration, is unknown. Then, the present study tested the effects of three weeks of AE (treadmill training at low intensity, 5x/week) beginning at the same day of bleomycin (intra-tracheally; 1,5 UI/Kg) administration. Eighty C57Bl/6 male mice were distributed in Control (Co), Exercise (Ex), Bleomycin (Bl) and Bleomycin+Exercise (Bl+Ex) groups. After three weeks of exercise, Bl+Ex group presented reduced number of total cells (p

Asthma is a chronic inflammatory airway disease, in which purinergic signaling has a central role, controlling activation of structural and hematopoietic cells. Aerobic exercise (AE) present anti-inflammatory effects to the airways, but no cellular and molecular mechanisms are known. Thus, this project evaluated the effects of AE on purinergic signaling response in a model of asthma induced by house dust mite (HDM). AE was performed in a treadmill at moderate intensity, 5x/week, during 4 weeks, after 3 weeks of prior HDM administration. HDM (dermatophagoides pteronyssinus; 100mg/mouse) was administered 3x/week, during 7 weeks. The results demonstrated that AE reduced ATP accumulation (p